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DME was tested in a heavy duty diesel engine and in an optically accessible high-temperature and pressure spray chamber in order to investigate and understand the effect of nozzle parameters on emissions, combustion and fuel spray concentration. The engine study clearly showed that smaller nozzle orifices were advantageous from combustion, efficiency and emissions considerations. Heat release analysis and fuel concentration images indicate that smaller orifices result in higher mixing rate between fuel and air due to reductions in the turbulence length scale, which reduce both the magnitude of fuel-rich regions and the steepness of fuel gradients in the spray, which enable more fuel to burn and thereby shorten the combustion duration.